One aim of the present proposal is to determine how evolution altered development to endow primates with an expanded cerebral cortex and a reduced limbic system (e.g., the olfactory bulb, septum, amygdala) compared with other mammals (e.g. rodents). Previous work has shown that cortical neurogenesis is protracted whereas neurogenesis in the limbic system is advanced in primates compared with rodents. However, these findings do not preclude the possibility that events prior to neurogenesis onset account for adult variations in the size of the cortex and limbic system across species. The expanded cerebral cortex and reduced limbic system of primates might emerge before neurogenesis begins. Specifically, I will test whether the expansion of the cerebral cortex in primates is due to changes in brain patterning and/or cell cycle kinetics. Another major aim of the present proposal is to use structural magnetic resonance imaging to examine the variation in brain region size of humans in adulthood. Compared with evolutionarily stable structures, structures with increased variability between species may also be more variable within a species. Individual variation likely comes with benefits (e.g., adaptive changes) as well as costs. For example, the abnormally large frontal cortex found in patients with autism may be indicative of an extreme end of a natural range. Understanding the developmental mechanisms that underlie the expansion of the brain in primates and its natural variation will enhance our understanding of the basic principles underlying adaptive and mal-adaptive changes in development. PUBLIC HEALTH RELEVANCE: Autism is associated with an enlargement of the cerebral cortex and reduction of some limbic structures. These developmental alterations might arise because of alterations in brain patterning or developmental timing but we currently understand very little about these neurological defects. Understanding how brains change in evolution will help elucidate how brains change mal-adaptively.